Racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide of formula (III), is a known substance which has been shown to possess anti-convulsant activity (Schutz, H. et al., Xenobiotica, 16, 769–778 (1986)), and was found to be the principal metabolite of the established anti-epileptic drug oxcarbazepine (formula IV). In addition to its anti-convulsant activity, racemic alcohol (III) can be readily synthesised in high yield by reduction of oxcarbazepine (IV), and thus serves as a useful intermediate for the preparation of optically pure (S)-(−)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (formula V) and (R)-(+)-10-acetoxy-10,11-dihydro-5H-dibenz/b,f/azepine-5-carboxamide (formula VI), two more recently disclosed, single-enantiomer anti-epileptic drugs demonstating improved biological properties (Benes, J. et al., J. Med. Chem., 42, 2582–2587 (1999)). The (S)-(−)-enantiomer (V) in particular has been shown to display a very favourable anti-convulsant profile.

A key step in the synthesis of either of the optically pure individual acetate esters (V) or (VI) involves the resolution of racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) into its individual, optically pure stereoisomers, (S)-(+)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (I) and (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II), which are the principal intermediates for synthesis of the optically pure acetates (V) and (VI). An improved method for this resolution was recently disclosed involving the efficient separation of diastereoisomeric tartrate half-esters of racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) (Learmonth, D., PCT/GB02/02176).
As mentioned above, racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) can be easily prepared by simple chemical reduction of the benzylic ketone group of oxcarbazepine (IV), by the use of, for example, metal hydrides in alcoholic medium. However, oxcarbazepine (IV) is an extremely expensive substance, and despite the very efficient resolution procedure (around 98% yield based on a single diastereoisomer), it should be noted that development of say only the (S)-(−)-acetate (V) would mean the loss of approximately 50% of very expensive material. It would thus be highly desirable to have a method of recycling this unwanted, but very expensive (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (II) which can be recovered from the resolution mixture. This recycling could be envisaged to involve a racemisation procedure, whereby the recovered but unwanted optically enriched (R)-(−)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide enantiomer (II) is converted into racemic (±)-10,11-dihydro-10-hydroxy-5H-dibenz/b,f/azepine-5-carboxamide (III) for re-introduction into the resolution cycle. The racemisation procedure should preferably involve the use of cheap, readily available solvents and reagents, and be operationally simple while affording good yields of pure, completely racemised product. However, in the case of alcohols (I) and (II), racemisation under standard acidic or basic conditions is unusually complicated, principally due to the very facile elimination of water from the molecules of (I) and (II), which leads exclusively to a dehydrated olefinic product of negligible interest for the synthesis of either (V) or (VI).